The invention relates to a method for the analysis of materials by chromatography and mass spectrometry. More specifically, the invention relates to a method for overcoming certain problems which have been found to exist when a gas-liquid chromatography column operating at varying temperatures is coupled to a mass spectrometer by means of a so-called open-split interface.
The ability of gas chromatography to separate mixtures, especially complex mixtures of biological origin, is well known. It is also well known that by coupling the output of a gas chromatography column to the input of a mass spectrometer, one can obtain mass spectra of the various components eluted from the column, thereby greatly facilitating the identification of these components.
One problem encountered in using such a combination of gas chromatography and mass spectrometry for analytical purposes is that gas chromatography columns normally operate at about atmospheric pressure, whereas of course, the ionization chamber of a mass spectrometer must operate at very low pressure. To enable the chromatography column to be coupled to the mass spectrometer, a so-called open-split interface may be used. Such an open-split interface comprises an intake conduit which is connected to the outlet of the chromatography column and an outlet conduit for connection to the inlet of a mass spectrometer. The outlet conduit connected to the inlet of the mass spectrometer is made of small diameter (being typically a platinum or glass capillary tube of 0.1-0.2 mm. internal diameter) so that the interface can operate at about atmospheric pressure while the ionization chamber connected to the outlet conduit of the interface can operate at low pressures without excessive pumping requirements. The open ends of the intake and outlet conduits are separated by a gap and the material leaving the intake conduit jumps this gap surrounded by an atmosphere of inert gas, which is supplied to the interface by a gas inlet conduit which enters the interface adjacent the gap. The inert gas is usually helium. A sleeve having two open ends may be provided surrounding the open ends of the intake and outlet conduits; this sleeve, constitutes an adequate open slit.
Further details of known open-split interfaces are described in the following papers, the disclosures of which are herein incorporated by reference:
D. Henneberg, U. Henrichs and G. Schromburg, J. Chromatogr. 112, 343 (1975); PA1 D. Henneberg, U. Henrichs and G. Schromburg, Chromatographia 8, 449 (1975); PA1 D. Henneberg, U. Henrichs, H. Hurmann and G. Schromburg, J. Chromatogr. 3, 147 (1980); PA1 H. J. Stan and B. Abraham, Anal. Chem. 50, 2161 (1978); and PA1 R. B. Hurley, J. High Res. Chromatogr. Chromatogr. Commun. 3, 147 (1980).
Open-split interfaces operate satisfactorily when the chromatography column is operating at a constant temperature. However, the resolution of very complex mixtures, usually of biological origin, can be greatly improved if the chromatography column is temperature-programmed, that is to say if the temperature at which the column operates is progressively increased during the course of each analysis from a lower temperature to an upper temperature. We have found that, if one attempts to use a temperature-programmed chromatography column with the open-split interfaces known hitherto, unreliable data can be obtained from the mass spectrometer because the base line signal of the total ionization monitor drifts so badly as to completely obscure the mass peaks or, at the least, sensitivity is sacrificed. Accordingly, there is a need for an open-split interface which can be used in conjunction with a temperature-programmed chromatography column and a mass spectrometer without causing severe drift in the total ionization monitor of the mass spectrometer. This invention provides such an open-split interface and a method for its use.